The relative importance of glomerular and tubular dynamics in the pathogenesis of indogenous and exogenous toxin- and circulatory-induced acute renal failure will be investigated using micropuncture, clearance, light and electron microscopic methods. The roles of various pharmacologic agents in prevention and treatment also will be evaluated. The initial portion of the study is to be devoted to the development of disease models in Munich Wistar rats that closely simulate the course of acute renal failure in man. Detailed functional and anatomic studies will be carried out in the pre-induction state and throughout the course of acute renal failure. Hemodynamics of individual surface glomeruli and peritubular vasculature will be investigated using servo-null pressure monitoring and micro-plasma protein analysis. Tubular function will be evaluated with pressure determinations and measurement of reabsorptive and secretory capacity using intratubular and peritubular perfusion. Simultaneous measurements of whole kidney blood flow and glomerular filtration will be performed. Plasma renin activity will be measured and the macula densa mechanism of glomerular filtration control will be evaluated by microperfusion while monitoring hemodynamics of the glomerulus. Light and electron microscopy will be performed on glomeruli and tubular segments during each period of study. Diuretics, adrenergic blockers and angiotensin inhibitors will be investigated for protective and therapeutic effects. The studies should provide more complete understanding of the pathogenesis of acute renal failure and will provide physiologic data that will aid in the control of human renal failure. BIBLIOGRAPHIC REFERENCES: Conger JD and Schrier RW: Pathogenesis and diagnosis of acute renal failure. In Pediatric Nephrology Symposium No. 4. Edited by Strauss O, New York, Plenum Press, 1977. Conger JD and Falk SA: Intrarenal dynamics in the pathogenesis and prevention of acute urate nephropathy. J. Clin. Invest. 59(5), 1977.